The present invention relates to a method and apparatus for the electrostatic application of powder material onto the surfaces of solid dosage forms, and more particularly, but not exclusively, pharmaceutical solid dosage forms.
A xe2x80x9csolid dosage formxe2x80x9d can be formed from any solid material that can be apportioned into individual units; it may be, but is not necessarily, an oral dosage form. Examples of pharmaceutical solid dosage forms include pharmaceutical tablets, pharmaceutical pessaries, pharmaceutical bougies and pharmaceutical suppositories. The term xe2x80x9cpharmaceutical tabletxe2x80x9d should be interpreted as covering all pharmaceutical products which are to be taken orally, including pressed tablets, pellets, capsules and spherules. Examples of non-pharmaceutical solid dosage forms include items of confectionery and washing detergent tablets.
The electrostatic application of powder material to solid dosage forms is known. In the known techniques, the powder is generally applied directly onto the solid dosage forms, either by spraying electrostatically charged powder material onto the solid dosage forms, or by holding the powder material at a potential difference to the solid dosage forms sufficient to cause the powder material to be attracted to the solid dosage forms. For example, WO92/14451 describes a process in which the cores of pharmaceutical tablets are conveyed on an earthed conveyor belt and electrostatically charged powder material is sprayed onto the tablet cores to form a powder coating on the exposed surface of the tablet cores. WO96/35516 describes a process in which the cores of pharmaceutical tablets are held substantially isolated from their surroundings adjacent to a source of powder at a potential difference to the tablet cores sufficient to cause the exposed surface of the tablet cores to become coated with the powder.
The present invention provides a method of electrostatically applying a powder material to a solid dosage form, the method comprising the steps of electrostatically applying a powder material to a first intermediate means, and transferring the powder material that has been applied to the first intermediate means from the first intermediate means to the solid dosage form.
Applying the powder material to a first intermediate means before it is applied to the solid dosage form has certain advantages. It becomes possible to provide an arrangement in which the location of the deposition of the powder material can be closely controlled and, for example, enables powder material to be deposited on a solid dosage form in a precise pattern. It may also facilitate the deposition of powder material on a three dimensional surface.
Any suitable method may be used to apply the powder material electrostatically to the first intermediate means. For example, the first intermediate means may be earthed and the powder material held at a potential sufficient to cause the powder material to adhere to the first intermediate means.
In a preferred embodiment of the invention the powder material is applied to the first intermediate means by applying an electrostatic charge to the first intermediate means, and holding the powder material at a potential sufficiently different from the potential of the first intermediate means to cause the powder material to adhere to the first intermediate means.
A first especially advantageous feature of a preferred embodiment of the invention is that the electrostatic charge may be applied to the first intermediate means in a pattern, making it possible to apply powder material onto a solid dosage form in the form of a pattern. Any desired pattern may be produced simply by applying a suitable electrostatic charge pattern to the first intermediate means. Thus, it is, for example, possible to print onto a solid dosage form the name or the dosage of the solid dosage form, or to apply to the solid dosage form a logo or some other design. By using different coloured powder materials, it is also possible to produce a pattern but at the same time have an uninterrupted coating on the solid dosage form. For example, different coloured powder materials could be used to produce a solid dosage form having a striped coating over all of the surface of a region of the solid dosage form or over the whole of the solid dosage form.
Where a coating is applied to parts only of a region being coated, the coating is referred to herein as discontinuous, even though in the case of, for example, joined up writing each part of the coating may be continuous with the other parts.
The electrostatic charge does not have to be applied to the first intermediate means in a pattern. It may be applied to the first intermediate means over the whole of a surface portion thereof. Accordingly, a conventional unpatterned and uninterrupted coating may be formed, if desired. Such a coating is referred to herein as a continuous coating but it will be understood that it may or may not, for example, cover all of a surface of a solid dosage form.
In the case where an electrostatic charge is applied to the first intermediate means, that means may be any means which is capable of maintaining an electrostatic charge on its surface. For example, the first intermediate means may be in the form of a drum or a belt and may comprise a photo-conductive semi-conductor at its surface. A photo-conductive semi-conductor is a material which conducts electricity on exposure to light, but behaves as an insulator in the absence of light. An electrostatic charge pattern may be applied to such a first intermediate means by electrostatically charging the semi-conductor in the dark, and then projecting an image onto the semi-conductor. The electrostatic charge will be dissipated in the illuminated areas, but will be retained in the unilluminated areas. Thus, an electrostatic charge pattern in the shape of the image will be formed on the semi-conductor. Such first intermediate means are used in conventional photocopiers as photo-conductive drums or belts. For example, a photoconductive drum used in the present invention may be a conductive drum coated with selenium, selenium/arsenic or selenium/tellurium, or a conductive drum coated with a thin layer of photoconductive pigment in a binder resin, and a charge transport layer coated over the photoconductive pigment layer. A photoconductive belt used for the invention may be a flexible conductive substrate coated with photogenerator layer comprising a photoconductive pigment in a binder polymer overcoated with a charge transport layer.
The powder material should possess a defined electrostatic charge which is either (a) of the same sign of charge as the residual charged area pattern on the photoconductive drum or belt after light exposure, or (b) of opposite sign of charge to the residual charged pattern on the photoconductive drum or belt after light exposure. In the case (a) the powder will be developed onto the areas of the photoconductive drum, or belt, which have been discharged, i.e. the light illuminated areas, and will be repelled by the areas of the photoconductive drum, or belt, which remain charged. Conversely in case (b) the powder will be developed onto the areas of the photoconductive drum, or belt, which remain charged, and will not be developed onto areas of the photoconductive drum, or belt, which have been discharged, i.e. the light illuminated areas. The powder material may have a permanent or temporary net charge. Any suitable method may be used to charge the powder material. Advantageously, the electrostatic charge on the powder material is imparted by a triboelectric charging process (as is common in conventional photocopying) or by corona charging.
Any suitable method may be used to apply the charged powder onto the first intermediate means. Methods have already been developed in the fields of electrophotography and electrography and examples of suitable methods are described, for example, in Electrophotography and Development Physics, Revised Second Edition, by L. B. Schein, published by Laplacian Press, Morgan Hill Calif.
A second especially advantageous feature of a preferred embodiment of the invention is that there is contact between the first intermediate means and the solid dosage form during transfer of the powder material from the intermediate to the solid dosage form. Contact between the first intermediate means and the solid dosage form increases the accuracy and speed and completeness with which the powder can be transferred to the dosage form. That may be advantageous irrespective of the method used to apply the powder material electrostatically to the first intermediate means. However, it is particularly advantageous where the powder material is applied in the form of a pattern.
The solid dosage form will, in general, be a three-dimensional object. For example, a conventionally-shaped pharmaceutical tablet comprises an upper domed surface and a lower domed surface, the two domed surfaces being joined together by an edge surface. In the known techniques where powder material is applied directly onto the solid dosage form, it is difficult to obtain uniform application of powder material, especially to the edges of the solid dosage form.
Accordingly, preferably, the first intermediate means conforms partially or completely to the shape of the solid dosage form on transfer of the powder material to the solid dosage form. In the case where the solid dosage form is a pressed tablet of domed shape the first intermediate means may conform only to the shape of the domed part of the tablet or may also contact the cylindrical side wall of the tablet.
If the first intermediate means is able to conform to the shape of the solid dosage form, it becomes possible to transfer powder material with greater uniformity to the edges of the solid dosage form. That may be advantageous irrespective of the method used to apply the powder material to the first intermediate means. Where the powder material has been applied to the first intermediate means in a discontinuous manner to form a pattern, it also becomes possible to reduce or even eliminate distortion of the pattern on transfer of the powder to the edges of the solid dosage form.
Any suitable method may be used to transfer powder material from the first intermediate means to the solid dosage form. The powder material that adheres to the first intermediate means may be transferred from the first intermediate means to the solid dosage form, at least partly, by electrostatic means. For example, the solid dosage form may be held at a potential sufficient to overcome the attractive forces of the powder material to the first intermediate means, and to cause the powder material to adhere to the solid dosage form instead. Alternatively, or in addition, the powder material that adheres to the first intermediate means may be transferred from the first intermediate means to the solid dosage form at least partly by heating the powder material during the transfer, and/or at least partly by means of pressurised contact between the first intermediate means and the solid dosage form.
If there is only one intermediate means, it must be possible to apply powder material electrostatically to that intermediate means, and to substantially transfer the powder material from that intermediate means to the solid dosage form. However, the properties required for the electrostatic application are not always compatible with the properties required for the transfer to the solid dosage form, particularly if the first intermediate means also has to be especially flexible.
Accordingly, a third especially advantageous feature of a preferred embodiment of the invention is that the powder material that has been applied to the first intermediate means is transferred from the first intermediate means to the solid dosage form via a second intermediate means. The first intermediate means then requires only those properties which are necessary for electrostatic application of the powder material to the first intermediate means, and the second intermediate means requires only those properties which are necessary to enable powder material to be transferred from the first intermediate means to the second intermediate means and from the second intermediate means to the solid dosage form.
Advantageously, there is contact between the first intermediate means and the second intermediate means on transfer of the powder material from the first intermediate means to the second intermediate means. Advantageously, there is contact between the second intermediate means and the solid dosage form on transfer of the powder material from the second intermediate means to the solid dosage form. More advantageously, the second intermediate means conforms partially or completely to the shape of the solid dosage form on transfer of the powder material to the solid dosage form. The second intermediate means may be in the form of a drum or a belt and may comprise an elastomeric material, for example a silicone rubber, that may be sufficiently soft to deform as required. Elastomeric materials used for the construction of the second intermediate means are, for example, rubber materials of defined durometer hardness. Durometer hardness can be described by the Shore A hardness scale. Materials particularly suitable would be, for example, silicone rubber with durometer hardness in the range 10A to 90A on the Shore A scale.
Electrostatic forces may also cause or contribute to the transfer of the powder material from the first intermediate means to the second intermediate means and/or from the second intermediate means to the solid dosage form.
Preferably, the method further comprises the step of treating the powder material to fix it on the solid dosage form. Where the powder material has been applied in a continuous manner, the treatment may result in the formation of a continuous coating on the solid dosage form.
The treatment of the powder material to secure it to the solid dosage form preferably involves a heating step, preferably using convection, but other forms of heating such as infra red radiation or conduction or induction may be used. The powder material should be heated to a temperature above its softening point, and then allowed to cool to a temperature below its glass transition temperature (Tg). Where the powder material has been applied in a discontinuous manner, it may be desirable to ensure that too much heat is not applied as the powder material may spread once it has fused, and that may result in distortion or even loss of the pattern. It is also important to control the amount of heat applied to avoid degradation of the powder material and/or the solid dosage form. The amount of heat required may be reduced by applying pressure to the powder material during the transfer step. Alternatively, the powder material may include a polymer which is cured during the treatment, for example, by irradiation with energy in the gamma, ultra violet or radio frequency bands.
The powder material may be treated to fix it on the solid dosage form as it is being transferred to the solid dosage form. For example, where there is contact between the solid dosage form and the first intermediate means or the second intermediate means on transfer of the powder material to the solid dosage form, fusing may be achieved by using the first intermediate means or the second intermediate means to apply heat with or without pressure to the solid dosage form. Alternatively, the treatment may be carried out after the powder material has been transferred to the solid dosage form.
The method may comprise the step of applying powder material to a first surface of the solid dosage form, and the subsequent step of applying powder material to a second surface of the solid dosage form. Such a step will usually be necessary if the whole surface of the dosage form is to be coated.
Preferably, the method is carried out as a continuous process.
The method of the present invention is not restricted to the use of any particular type of powder material. The powder materials described in PCT/GB96/01101 are examples of suitable powder materials.
The powder material may include an active material, for example a biologically active material, that is, a material which increases or decreases the rate of a process in a biological environment. The biologically active material may be one which is physiologically active.
Conventionally, where an active material is to be administered in solid dosage form, the active material is mixed with a large volume of non-active xe2x80x9cfillerxe2x80x9d material in order to produce a dosage form of manageable size. It has been found, however, that it is difficult to control accurately the amount of active material contained in each dosage form, leading to poor dose uniformity. That is especially the case where the required amount of active material in each dosage form is very low.
By electrostatically applying active material to a dosage form, it has been found to be possible to apply accurately, and reproducibly, very small amounts of active material to the dosage form, leading to improved dose reproducibility.
The powder material comprising active material may be applied to a solid dosage form containing the same or a different active material, or may be applied to a solid dosage form containing no active material.
The present invention further provides an apparatus for electrostatically applying a powder material to a solid dosage form, the apparatus comprising means for applying a powder material to a first intermediate means, and means for transferring the powder material that has been applied to the first intermediate means from the first intermediate means to the solid dosage form, or a means for transferring the powder material that has been applied to the first intermediate means from the first intermediate means to a second intermediate means and means for transferring the powder material subsequently from the second intermediate means to the solid dosage form.
The apparatus of the invention may be in a form suitable for carrying out the method of the invention in any of the forms described above.